The goal of this project is to determine whether there exist chronic alterations in blood composition which are linked to blood hyperviscosity and recurrent stroke. Evidence from cross sectional measurements indicates that low serum albumin and elevations in fibrinogen, leucocytes, and blood viscosity are interrelated, but the duration of these alterations and their relationship to stroke recurrence are not known. Several lines of both clinical and biochemical evidence suggest that impaired glucose tolerance contributes to blood hyperviscosity. Interleukins 1 and 6, by regulating fibrinogen and albumin biosynthesis, are likewise thought to contribute to viscous abnormalities. The specific aims of this proposal will test the hypotheses that 1) chronic blood hyperviscosity exists and contributes to recurrent stroke; 2) impaired glucose tolerance contributes to hyperviscosity; 3) interleukins 1 and 6 are humoral mediators of hyperviscosity; and 4) hyperviscosity variables may be improved with treatment. The evaluate these hypotheses a longitudinal study of subjects grouped according to the presence or absence of hyperviscosity will be conducted. The incidence of the clinical endpoints of recurrent stroke, myocardial infarction, and vascular death in the two groups will be compared. Longitudinal measurements of whole blood, plasma, and serum viscosity, glycated hemoglobin, and urinary microalbumin will be made, and in pilot studies interleukins 1 and 6 and plasma free insulin will be measured.